Desferrioxamine mesylate (deferoxamine) used in the treatment of hepatocellular carcinoma was tested for anti-HIV activity. Some of the hepato cellular carcinoma cell lines contain integrated HBV which has an unusual reverse transcription step in its replication and this prompted us to test DFX for antiretroviral properties. H9 cells were infected with HTLV-IIIB and treated with varying concentrations of the drug. At day 7, coded samples of DNA were tested for HIV DNA by PCR. DFX inhibited the expression of p24 antigen and substantially reduced detectable levels of HIV DNA and antigen. The inhibition was dose dependant, with 30 uM DFX being effective as 187 uM AZT. Viability was greater than 70% at day 7 in all cultures. Three independent experiments were done with similar results for p24 expression. The observation of in vitro inhibition of HIV-1 by DFX suggests a new mechanism of viral inhibition. Further studies are being conducted to address this question as well as to ascertain possible synergy with other agents currently in clinical trials.